Wang Hong-Hui, Zhang Kun-Huan, Wu Si-Le, Pan Meng-Hao, Li Xiao-Han, Sun Shao-Chen
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Center of Reproductive Medicine, The Affiliated Weihai Second Municipal Hospital of Qingdao University, Weihai 264200, China.
Development. 2025 Sep 1;152(17). doi: 10.1242/dev.204665. Epub 2025 Sep 2.
Successful fertilization is important for early embryo development and offspring generation. Cortical granules, which are formed in the cytoplasm, are transported to the cortex to avoid polyspermy, which prevents sperm penetration into oocytes. The underlying mechanism is still largely unknown. In this study, we have identified that GTPase Rab10-mediated vesicles play a pivotal role in actin dynamics, which regulate cortical granule transport and ZP2 function in mouse and porcine oocytes. We found that Rab10 accumulated at the mouse and porcine oocyte cortex and modulated the RhoA pathway to control actin dynamics. Disrupting the functions of Rab10 affected myosin Va expression, which impaired cortical granule movement to the cortex, causing an insufficient supply of cortical granule contents and weakened zona pellucida modification. In addition, overexpression of GDP-bound Rab10 led to ZP2 downregulation and accumulation at the cortex, which affected zona pellucida reaction. Taken together, our findings demonstrate that Rab10 regulates the RhoA pathway for actin dynamics and the myosin Va complex for the cortical granule-based cortical reaction, and the Rab10-ZP2 complex contributes to the ZP2 supply that is necessary for the zona pellucida reaction.
成功受精对于早期胚胎发育和后代产生至关重要。皮质颗粒在细胞质中形成,被运输到皮质以避免多精受精,从而防止精子穿透卵母细胞。其潜在机制在很大程度上仍不清楚。在本研究中,我们确定GTP酶Rab10介导的囊泡在肌动蛋白动力学中起关键作用,肌动蛋白动力学调节小鼠和猪卵母细胞中的皮质颗粒运输和ZP2功能。我们发现Rab10在小鼠和猪卵母细胞皮质积累,并调节RhoA途径以控制肌动蛋白动力学。破坏Rab10的功能会影响肌球蛋白Va的表达,这会损害皮质颗粒向皮质的移动,导致皮质颗粒内容物供应不足以及透明带修饰减弱。此外,结合GDP的Rab10的过表达导致ZP2下调并在皮质积累,这影响了透明带反应。综上所述,我们的研究结果表明,Rab10调节RhoA途径以控制肌动蛋白动力学,并调节肌球蛋白Va复合物以介导基于皮质颗粒的皮质反应,并且Rab10-ZP2复合物有助于透明带反应所需的ZP2供应。